Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

Abstract

Fusion genes (FGs) are major molecular biological abnormalities in hematological malignancies and have become well-established molecular markers for disease classification, risk stratification, and targeted therapies. The long tail phenomenon is observed in the distribution of FGs, which means that except for dozens of the most common FGs, the positive rates of the other FGs are all below 1%, even if they have been frequently reported in the literature. However, the total positive rate of these singly relatively rare FGs is actually not low due to their wide variety and numerous members. We therefore put forward the conception "fusion gene family, FG-FM" to describe fusions that share one common protagonist gene with different partner genes. Most of the FGs in hematological malignancies discovered to date can be classified into about 20 major families. Based on the characteristics of the currently reported FGs, it can be expected that although a great many FGs may be identified in the future, the total number of FG-FMs is rather limited. FGs in the same FG-FM often have similarities in pathogenicity, clinical features, and treatment outcomes. Classifying FGs according to FG-FMs will aid in understanding their pathogenicity and optimizing detection schemes.

CTCF: A novel fusion partner of ETO2 in a multiple relapsed acute myeloid leukemia patient

“…ETO2 indirectly promoted leukemia stem cells transformation and guided a relapse gene program which induced dismal clinical outcomes in AML 6 . To our knowledge, five ETO2 fusion genes have been reported in hematological malignancies up to date, including inv(16)(p13.3q24.3)/ ETO2‐GLIS2 , 7,8 t(1;16)(p31;q24)/ NFIA‐ETO2 , 9 and t(16;21)(q22;q24)/ RUNX1‐ETO2 10 in AML, t(9;16)(p13;q24)/ PAX5‐ETO2 11 in ALL and t(14;16)(q32;q24)/ IGH‐ETO2 12 in lymphoma. Here, we describe the first case presenting as AML with novel CTCF‐ETO2 and ETO2‐CTCF chimeric genes.…”

CTCF, a novel fusion partner of ETO2 in a post-transplant relapsed acute myeloid leukemia patient

“…ETO2 indirectly promoted leukemia stem cells transformation and guided a relapse gene program which induced dismal clinical outcomes in AML [8]. To our knowledge, ve ETO2 fusion genes have been reported in hematological malignancies up to date, including inv(16)(p13.3q24.3)/ETO2-GLIS2 [2,9],t(1;16) (p31;q24)/NFIA-ETO2 [10] and t(16;21)(q22;q24)/RUNX1-ETO2 [11] in AML, t(9;16)(p13;q24)/PAX5-ETO2 [12] in ALL and t(14;16)(q32;q24)/IGH-ETO2 [13] in lymphoma. Here we describe the rst case presenting as AML with novel CTCF-ETO2 and reciprocal chimeric genes.…”

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center

“…Several groups have discovered numerous novel FGs, such as those involving ZNF384 , MEF2D , PAX5 , and DUX4 rearrangements, among cases that were once regarded as B-other-ALL with no defining cytogenetic abnormalities [ 4 – 9 ]. To better understand the incidences of FGs and their pathological characteristics, we proposed the conception of the “fusion gene family, FG-FM” to classify fusions that involve one protagonist gene and various fusion partners [ 10 ]. FGs in the same family often share commonalities in pathogenicity, clinical features, and treatment outcomes.…”